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Compositions and methods for the prevention and treatment of cancer

A cancer, complex technology, applied in the therapeutic field of cancer prevention and treatment, can solve the problems of expansion of circulating cytotoxic T cell lymphocytes, inability to produce costimulatory molecules, failure of cancer immunotherapy strategies, etc.

Inactive Publication Date: 2013-08-21
UTI LLP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, strategies to induce tumor-specific immunity in patients have not been successful so far
Multiple factors contribute to failure of existing cancer immunotherapy strategies, study suggests
First, these strategies fail to adequately expand circulating cytotoxic T cell lymphocytes
Second, cancer patients are often immunosuppressed and unable to produce co-stimulatory molecules necessary to initiate an immune response

Method used

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  • Compositions and methods for the prevention and treatment of cancer
  • Compositions and methods for the prevention and treatment of cancer
  • Compositions and methods for the prevention and treatment of cancer

Examples

Experimental program
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preparation example Construction

[0142] Nanoparticles can be formed by contacting an aqueous phase containing antigen / MHC / co-stimulatory molecule complexes and polymers with a non-aqueous phase, followed by evaporation of the non-aqueous phase to allow aggregation of the particles in the aqueous phase, As taught in US Patent No. 4,589,330 or 4,818,542. Preferred polymers for this preparation method are natural or synthetic copolymers or polymers selected from the group consisting of gelatin agar, starch, arabinogalactan, albumin, collagen, polyglycolic acid, polylactic acid, glycolide -L(-)-lactide poly(ε-caprolactone, poly(ε-caprolactone-CO-lactic acid) copolymer, poly(ε-caprolactone-CO-glycolic acid) copolymer, poly( β-hydroxybutyrate), poly(ethylene oxide), polyethylene, poly(alkyl-2-cyanoacrylate), poly(hydroxyethyl methacrylate), polyamide, polyamino acid, poly(2 -hydroxyethyl DL-asparagine), polyester urea, poly(L-phenylalanine / ethylene glycol / 1,6-hexamethylene diisocyanate) and poly(methyl methacrylat...

Embodiment 1

[0171]Synthesis and characterization of gold-based pMHC-NPs. Gold nanoparticles (GNPs) of specific sizes can be synthesized according to Levy, R. et al. ("Rational and combinatorial design of peptide capping ligands for gold nanoparticles." J Am Chem Soc 126, 10076-84 (2004)). The size, density, charge and monodispersity of the GNP preparations were measured using a spectrophotometer, transmission electron microscopy (TEM) and dynamic light scattering. Then, GNP samples were concentrated and conjugated to pHMC (antigen-MHC complexes) using different methods. Developed for quantification of pMHC valence / GNP and for high concentration (~10 14 / ml) method of concentrating antigen=MHC-GNP without disrupting monodispersity ( figure 1 ).

Embodiment 2

[0173] pMHC binding capacity of GNP. Two methods were used to coat pMHC onto GNPs of different sizes: (i) random binding of pMHC to GNPs through electrostatic interactions; and (ii) sulfhydryl-PEG-NH 2 Linker-directed binding. In this case, additional thiol-PEG was used as a GNP stabilizer to prevent aggregation. It is contemplated that the first approach would result in very high ligand densities, destroying the specificity of pMHC binding (ie, only a fraction of pMHC can be recognized by cognate T cells). The second approach aims to generate pMHC-GNPs that carry less pMHC but bind directionally through their C-terminus. Both methods were tested against 14nm GNP and 40nm GNP. The pHMC binding capacity of GNPs was confirmed to be a function of surface area for both methods. Therefore, when the nanoparticle size is larger, more pMHC is bound. Unexpectedly, it was found that PEG-mediated binding not only ensures the directionality of binding but also enhances the binding ca...

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Abstract

Conventional cancer immunotherapy falls short at efficiently expanding T cells that specifically target cancerous cells in numbers sufficient to significantly reduce the tumor size or cancerous cell number in vivo. To overcome this limitation, provided herein are nanoparticles coated with MHC class I and / or class II molecules presenting tumor-specific antigens and co-stimulatory molecules and their use to expand antigen-specific anti-tumorigenic T cellsto levels not achieved in current immunotherapeutic techniques. These antigen-specific anti-tumorigenic T cells include cytotoxic T cells, effector T cells, memory T cells, and helper T cells that are necessary to initiate and maintain a substantial immune response against metastatic or non- metastatic cancerous, pre-cancerous, or neoplastic cells in vivo.; The present invention describes a systemic approach to targeting cancerous or pre-cancerous cells that are circulating cells, as in lymphomas, migratory metastatic cells, and solid tumors.

Description

[0001] Cross References to Related Applications [0002] Pursuant to 35 U.S.C. §119(e), this application claims priority to U.S. Provisional Application Serial No. 61 / 413,330, filed November 12, 2010, which is hereby incorporated by reference in its entirety. technical field [0003] The present invention relates to compositions and methods related to immunotherapy and medicine. In particular, the present invention relates to therapeutic methods for the prevention and treatment of cancer. Background technique [0004] Cancer immunity is an emerging field in cancer therapy that aims to harness the body's own immune defenses to target and eliminate cancer cells. The idea of ​​using the body's own immune system to attack cancer cells has many advantages over traditional therapies that are site-specific, such as radiation and surgery, or chemotherapy, which comes with harmful side effects and high toxicity. [0005] Significant progress has been made in the field through the i...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61P35/00
CPCA61K38/17A61K39/0011A61K47/6923A61K47/6929A61K47/62A61P35/00A61P35/04A61P37/04A61P43/00A61K47/50A61K47/30A61K39/395
Inventor 佩蕾·圣玛丽亚
Owner UTI LLP
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